Thrombosis induced by purely local vascular injury can be readily contained by normal compensatory mechanisms: only when these mechanisms are overwhelmed or destroyed by a more generalized reaction can thrombosis proceed. Moreover, to make platelet aggregation irreversible thrombin is necessary, and to cause massive propagation of the thrombus, the elaboration of fibrin is required. In both of these latter roles, activation of the clotting mechanism appears essential. Thus, even if clotting factors do not serve as trigger mechanisms in the initiation of intravascular coagulation, they may be important in the fixation and growth of the thrombus. It is for these reasons that we have chosen to work in the area of fibrin formation. Our long term goals are to correlate in vitro and in vivo clotting reactions, to obtain a better understanding of thrombogenesis, to search for acceptable evidence of hypercoagulability, and to improve antithrombotic therapy.